RETRACTED: Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial

Abstract

Summary Background C-kit+ lineage− cardiac stem cells (CSCs) improve postinfarction left ventricular (LV) dysfunction in animals; however, their efficacy in humans is unknown. Methods In February 2009, we began SCIPIO (Stem Cell Infusion in Patients with Ischemic CardiOmyopathy), a Phase I, randomized, open-label trial of CSCs in patients with postinfarction LV dysfunction (ejection fraction [EF] ≤ 40%) who underwent coronary bypass surgery. Autologous CSCs were isolated from the right atrial appendage and re-infused intracoronarily 4 ± 1 months after surgery; controls received no treatment. In Stage A, 9 treated and 4 control patients were consecutively enrolled to assess the feasibility and short-term safety of CSCs. Then, in Stage B, patients were randomized to the treated or control arm in a 2:3 ratio using a block randomization scheme and a block size of five. Primary (safety) and secondary (efficacy) endpoints were assessed at serial times after enrollment. Findings Autologous CSCs were successfully isolated and expanded in 80 out of 81 patients. In 16 treated patients, no CSC-related adverse effects have been observed. LVEF (3D echocardiography) increased from 30.3 ± 1.9% before CSC infusion to 38.5 ± 2.8% at 4 months after infusion, (P=0.001, n=14). This was associated with an improvement in regional wall motion score index (echocardiography) (1.91 ± 0.09 vs. 1.73 ± 0.09, P=0.005), NYHA functional class (2.19 ± 0.16 vs. 1.63 ± 0.16, P=0.003), and quality of life (MLHFQ score, 46.44 ± 5.22 vs. 26.69 ± 4.92, P<0.0001). In contrast, in 7 control patients, none of these variables changed appreciably during the corresponding time-interval. Importantly, the salubrious effects of CSCs were even more pronounced at 1 year (e.g., LVEF increased by 12.3 ± 2.1% vs. pre-CSCs, P=0.0007, n=8), suggesting that CSCs continue to improve LV function beyond the first 4 months. In the 7 treated patients in whom cardiac magnetic resonance (cMR) imaging could be performed, infarct size decreased by 7.8 ± 1.7 g (23.8%) at 4 months (P=0.004) and 9.8 ± 3.5 g (30.3%) at 1 year (P=0.04). Interpretation These initial results in humans are very encouraging, and suggest that infusion of autologous CSCs is effective in improving LV systolic function and reducing infarct size in patients with heart failure.